A mitogenic synthetic polynucleotide suppresses LPS-O polysaccharide specific antibody response
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Unmethylaled bacterial DNA is mitogenic and induces T-cell independent murine Bcell prolifration. These stimulatory effects are also induced by synthetic oligonucleotides that contain one or more unmethylated CpG dinucleotides (CpG oligo). Such mitogenicity is nol seen with highly-methylated vertebrate DNA, which has a low prevalence of the CpG motif. Mitogenic bacterial DNA has been hypothesized to give immunologie advantage to host defense against bacterial infection. The stimulatory effects of bacterial DNA and CpG oligo have also been proposed as vaccine adjuvants. In order to determine if a synthetic CpG oligo that was stimulatory in vitro could augment the murine antibody response to bacterial polysaccharides (Pseudomonas aeruginosa LPS-O polysaccharide side chain; high MW PS), BALB/C mice were administered 500 ug or 250 ug of CpG oligo simultaneously with high MW PS, and antibody tilers were measured by ELISA weekly for 4 weeks. Controls received saline, non-CpG oligo plus PS, oligo alone, or PS alone. Despite an increase in total IgM in CpG oligo-treated mice, CpG oiigo treatment plus PS significantly decreased the high MW PS antibody response compared to PS alone. By contrast, mice treated with non-CpG oligo plus PS had antibody responses similar to PS alone. We conclude that, despite previous in vitro and current in vivo evidence of B-cell proliferation, this CpG oligo reduces PS specific antibody responses in an animal model. Based on results in this model, these reagents may not be useful adjuvants for bacterial PS vaccines. Further studies are in progress to examine the mechanism of CpG oligo-mediated inhibition of PS-specific antibody response.
